Worsened skin symptoms such as wrinkles, age spots, dullness, and sagging, which are caused by factors such as increasing age, stress, and ultraviolet rays exposure, are very easily recognized by appearance as aging signs. Therefore, people have a very strong interest in skin aging phenomena, and various means have been developed for the purpose of maintaining the appearance of the skin beautifully.
Wrinkles are one of skin aging phenomena. However, at present, the mechanism of wrinkle formation has not yet been completely elucidated because the mechanism is complicated and the experimental reproduction is very difficult. Examples of the mechanism of wrinkle formation include cellular damages due to ultraviolet rays and the like and cellular apoptosis enhanced by the damages, hydrolysis of fiber components such as collagen due to increases in expression of proteases such as matrix metalloproteases (MMPs), and fiber bundle disorganization due to increased cytokines. In particular, MMPs have a variety of functions such as degrading the extracellular matrix formed of collagen, proteoglycan, elastin, and the like, and degrading proteins expressed on the surface of cells, and include a large number of subtypes. MMP1 degrades type I collagen and type III collagen as major components of the skin dermal matrix. MMP2 and MMP9 degrade type IV collagen and laminin as basement membrane components and elastin as a dermal matrix component, for example. MMP3 and MMP10 degrade proteoglycan, type IV collagen, and laminin, for example. Those degradation actions cause the decrease and degeneration of the extracellular matrix, which are recognized as one of important factors for the formation of wrinkles, sagging, and the like in the skin (see Patent Literature 1). Further, inflammatory cytokines such as TNF-α, IL-1, and IL-6 are known to be involved in the formation of wrinkles and sagging through the induction of the production of MMPs (see Patent Literature 2). As described above, those factors, which are strongly involved in skin aging phenomena such as wrinkles and sagging, are far from independent factors and also supposedly influence each other. Such situation makes the mechanism of wrinkle formation complicated.
It is widely known that retinoic acid exhibits an effect of reducing wrinkles, which are one of skin aging phenomena and occur as a result of photoaging due to irradiation with ultraviolet rays (see Non Patent Literature 1). In the United States, retinoic acid has been approved as a pharmaceutical agent for the treatment of wrinkles and acnes, and has been used as a drug for the rejuvenation of the skin in a large number of patients. In contrast, in Japan, retinoic acid has not been approved because of its problems in terms of safety such as irritation to the skin. Further, some attempts have been made on reducing wrinkles using a blend of collagen and hyaluronic acid (see Patent Literatures 3 and 4), and besides, ascorbic acid (see Patent Literature 5), tocopherol (see Patent Literature 6), or the like is known as the wrinkle-reducing agent. However, no wrinkle-reducing material that gives sufficiently satisfactory results has been found for, for example, the following reasons: the wrinkle-reducing agent does not have any sufficient wrinkle-reducing effect; and the wrinkle-reducing agent may cause problems in terms of safety or stability such as expression of an undesired drug effect at a concentration at which a wrinkle-reducing effect is expressed. Thus, there has been a strong demand for the development of a novel wrinkle-reducing agent.
With regard to amino acids, there are a large number of amino acids including naturally-occurring and non-naturally-occurring amino acids. Those amino acids are known to serve as functional polymers responsible for the maintenance of biological structures and biological reactions, and besides, to exhibit various bioactivities. The naturally-occurring amino acids or derivatives thereof are expected to have not only bioactivities but also high safety, and are thus widely employed in the fields of foods, cosmetics, and pharmaceutical agents, for example. In particular, in the field of cosmetics, it is known that alanine exhibits a skin-whitening action (see Patent Literature 7), an α-amino acid derivative exhibits a parakeratosis inhibitory action, a pore-shrinking action, or a rough skin-preventing/ameliorating action (see Patent Literature 8), a cysteic acid or homocysteic acid exhibits a skin desquamation-promoting or epidermal renewal-stimulating action (see Patent Literature 9), an N-acyl amino acid exhibits a hair growth-promoting action and a moisture-retaining action (see Patent Literature 10), and an essential amino acid such as glutamine exhibits a cell-stimulatory action (see Patent Literature 11). Further, alanine is known to have a wrinkle-reducing action (see Patent Literature 12).